ID   URE23_HELPY             Reviewed;         238 AA.
AC   P14916;
DT   01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-1992, sequence version 2.
DT   27-MAR-2024, entry version 174.
DE   RecName: Full=Urease subunit alpha {ECO:0000255|HAMAP-Rule:MF_01955};
DE            EC=3.5.1.5 {ECO:0000255|HAMAP-Rule:MF_01955};
DE   AltName: Full=Urea amidohydrolase subunit alpha {ECO:0000255|HAMAP-Rule:MF_01955};
GN   Name=ureA {ECO:0000255|HAMAP-Rule:MF_01955}; Synonyms=hpuA;
GN   OrderedLocusNames=HP_0073;
OS   Helicobacter pylori (strain ATCC 700392 / 26695) (Campylobacter pylori).
OC   Bacteria; Campylobacterota; Epsilonproteobacteria; Campylobacterales;
OC   Helicobacteraceae; Helicobacter.
OX   NCBI_TaxID=85962;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=CPM630;
RX   PubMed=2326167; DOI=10.1093/nar/18.2.362;
RA   Clayton C.L., Pallen M.J., Kleanthous H., Wren B.W., Tabaqchali S.;
RT   "Nucleotide sequence of two genes from Helicobacter pylori encoding for
RT   urease subunits.";
RL   Nucleic Acids Res. 18:362-362(1990).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=85P;
RX   PubMed=2001995; DOI=10.1128/jb.173.6.1920-1931.1991;
RA   Labigne A., Cussac V., Courcoux P.;
RT   "Shuttle cloning and nucleotide sequences of Helicobacter pylori genes
RT   responsible for urease activity.";
RL   J. Bacteriol. 173:1920-1931(1991).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=HPK5;
RX   PubMed=10844692; DOI=10.1046/j.1365-2958.2000.01918.x;
RA   Akada J.K., Shirai M., Takeuchi H., Tsuda M., Nakazawa T.;
RT   "Identification of the urease operon in Helicobacter pylori and its control
RT   by mRNA decay in response to pH.";
RL   Mol. Microbiol. 36:1071-1084(2000).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 700392 / 26695;
RX   PubMed=9252185; DOI=10.1038/41483;
RA   Tomb J.-F., White O., Kerlavage A.R., Clayton R.A., Sutton G.G.,
RA   Fleischmann R.D., Ketchum K.A., Klenk H.-P., Gill S.R., Dougherty B.A.,
RA   Nelson K.E., Quackenbush J., Zhou L., Kirkness E.F., Peterson S.N.,
RA   Loftus B.J., Richardson D.L., Dodson R.J., Khalak H.G., Glodek A.,
RA   McKenney K., FitzGerald L.M., Lee N., Adams M.D., Hickey E.K., Berg D.E.,
RA   Gocayne J.D., Utterback T.R., Peterson J.D., Kelley J.M., Cotton M.D.,
RA   Weidman J.F., Fujii C., Bowman C., Watthey L., Wallin E., Hayes W.S.,
RA   Borodovsky M., Karp P.D., Smith H.O., Fraser C.M., Venter J.C.;
RT   "The complete genome sequence of the gastric pathogen Helicobacter
RT   pylori.";
RL   Nature 388:539-547(1997).
RN   [5]
RP   PROTEIN SEQUENCE OF 1-20.
RX   PubMed=2318539; DOI=10.1128/iai.58.4.992-998.1990;
RA   Hu L.-T., Mobley H.L.T.;
RT   "Purification and N-terminal analysis of urease from Helicobacter pylori.";
RL   Infect. Immun. 58:992-998(1990).
RN   [6]
RP   PROTEIN SEQUENCE OF 1-20, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL
RP   PROPERTIES, AND INTERACTION WITH UREB.
RX   PubMed=2188975; DOI=10.1016/s0021-9258(19)38872-6;
RA   Dunn B.E., Campbell G.P., Perez-Perez G.I., Blaser M.J.;
RT   "Purification and characterization of urease from Helicobacter pylori.";
RL   J. Biol. Chem. 265:9464-9469(1990).
RN   [7]
RP   PROTEIN SEQUENCE OF 1-20.
RC   STRAIN=ATCC 43504 / NCTC 11637 / JCM 7653 / RPH 13487;
RX   PubMed=1452359; DOI=10.1128/iai.60.12.5259-5266.1992;
RA   Turbett G.R., Hoej P.B., Horne R., Mee B.J.;
RT   "Purification and characterization of the urease enzymes of Helicobacter
RT   species from humans and animals.";
RL   Infect. Immun. 60:5259-5266(1992).
RN   [8]
RP   DISRUPTION PHENOTYPE.
RC   STRAIN=85P;
RX   PubMed=1313413; DOI=10.1128/jb.174.8.2466-2473.1992;
RA   Cussac V., Ferrero R.L., Labigne A.;
RT   "Expression of Helicobacter pylori urease genes in Escherichia coli grown
RT   under nitrogen-limiting conditions.";
RL   J. Bacteriol. 174:2466-2473(1992).
RN   [9]
RP   CATALYTIC ACTIVITY.
RX   PubMed=1612735; DOI=10.1128/iai.60.7.2657-2666.1992;
RA   Hu L.-T., Foxall P.A., Russell R., Mobley H.L.T.;
RT   "Purification of recombinant Helicobacter pylori urease apoenzyme encoded
RT   by ureA and ureB.";
RL   Infect. Immun. 60:2657-2666(1992).
RN   [10]
RP   FUNCTION.
RX   PubMed=8039935; DOI=10.1128/iai.62.8.3586-3589.1994;
RA   Tsuda M., Karita M., Morshed M.G., Okita K., Nakazawa T.;
RT   "A urease-negative mutant of Helicobacter pylori constructed by allelic
RT   exchange mutagenesis lacks the ability to colonize the nude mouse
RT   stomach.";
RL   Infect. Immun. 62:3586-3589(1994).
RN   [11]
RP   SUBCELLULAR LOCATION.
RX   PubMed=8641799; DOI=10.1128/iai.64.3.905-912.1996;
RA   Phadnis S.H., Parlow M.H., Levy M., Ilver D., Caulkins C.M., Connors J.B.,
RA   Dunn B.E.;
RT   "Surface localization of Helicobacter pylori urease and a heat shock
RT   protein homolog requires bacterial autolysis.";
RL   Infect. Immun. 64:905-912(1996).
RN   [12]
RP   INDUCTION.
RX   PubMed=11447165; DOI=10.1128/iai.69.8.4891-4897.2001;
RA   van Vliet A.H.M., Kuipers E.J., Waidner B., Davies B.J., de Vries N.,
RA   Penn C.W., Vandenbroucke-Grauls C.M.J.E., Kist M., Bereswill S.,
RA   Kusters J.G.;
RT   "Nickel-responsive induction of urease expression in Helicobacter pylori is
RT   mediated at the transcriptional level.";
RL   Infect. Immun. 69:4891-4897(2001).
RN   [13]
RP   REVIEW ON VIRULENCE OF H.PYLORI.
RX   PubMed=17313591; DOI=10.1111/j.1574-6968.2007.00648.x;
RA   Clyne M., Dolan B., Reeves E.P.;
RT   "Bacterial factors that mediate colonization of the stomach and virulence
RT   of Helicobacter pylori.";
RL   FEMS Microbiol. Lett. 268:135-143(2007).
RN   [14]
RP   X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS), SUBUNIT STRUCTURE, AND PH
RP   DEPENDENCE.
RX   PubMed=11373617; DOI=10.1038/88563;
RA   Ha N.-C., Oh S.-T., Sung J.Y., Cha K.A., Lee M.H., Oh B.-H.;
RT   "Supramolecular assembly and acid resistance of Helicobacter pylori
RT   urease.";
RL   Nat. Struct. Biol. 8:505-509(2001).
CC   -!- FUNCTION: Ammonia produced by ureolysis increases the gastric pH
CC       thereby providing an environment permissive for colonization of the
CC       stomach. {ECO:0000269|PubMed:8039935}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=2 H(+) + H2O + urea = CO2 + 2 NH4(+); Xref=Rhea:RHEA:20557,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16199,
CC         ChEBI:CHEBI:16526, ChEBI:CHEBI:28938; EC=3.5.1.5;
CC         Evidence={ECO:0000255|HAMAP-Rule:MF_01955,
CC         ECO:0000269|PubMed:1612735, ECO:0000269|PubMed:2188975};
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=0.48 mM for urea {ECO:0000269|PubMed:2188975};
CC         Vmax=1.1 mmol/min/mg enzyme {ECO:0000269|PubMed:2188975};
CC       pH dependence:
CC         Optimum pH is 8.0. Active from pH 4.0 to 10.0. In unbuffered
CC         solutions, the dodecameric complex is active at pH 3.0.
CC         {ECO:0000269|PubMed:11373617, ECO:0000269|PubMed:2188975};
CC   -!- PATHWAY: Nitrogen metabolism; urea degradation; CO(2) and NH(3) from
CC       urea (urease route): step 1/1. {ECO:0000255|HAMAP-Rule:MF_01955}.
CC   -!- SUBUNIT: Heterohexamer of 3 UreA (alpha) and 3 UreB (beta) subunits.
CC       Four heterohexamers assemble to form a 16 nm dodecameric complex.
CC       {ECO:0000255|HAMAP-Rule:MF_01955, ECO:0000269|PubMed:11373617}.
CC   -!- INTERACTION:
CC       P14916; P69996: ureB; NbExp=2; IntAct=EBI-7737170, EBI-7566591;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_01955,
CC       ECO:0000269|PubMed:8641799}. Note=Also associates with the outer
CC       membrane upon autolysis of neighboring bacteria.
CC   -!- INDUCTION: By nickel ions. {ECO:0000269|PubMed:11447165}.
CC   -!- DISRUPTION PHENOTYPE: Cells do not express urease.
CC       {ECO:0000269|PubMed:1313413}.
CC   -!- MISCELLANEOUS: The novel dodecameric structure of the enzyme may allow
CC       it to remain active at the cell surface at acidic gastric pH. Within
CC       this dodecameric structure the 12 active sites are clustered within the
CC       interior of the proteinaceous shell. This may allow a high local
CC       concentration of ammonia within the enzyme which may protect the
CC       nickel-chelating groups from protonation.
CC   -!- SIMILARITY: In the N-terminal section; belongs to the urease gamma
CC       subunit family. {ECO:0000255|HAMAP-Rule:MF_01955}.
CC   -!- SIMILARITY: In the C-terminal section; belongs to the urease beta
CC       subunit family. {ECO:0000255|HAMAP-Rule:MF_01955}.
CC   -!- CAUTION: The orthologous protein is known as the gamma/beta subunit
CC       (UreAB) in most other bacteria. {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=Protein Spotlight; Note=Going unnoticed - Issue 95
CC       of June 2008;
CC       URL="https://web.expasy.org/spotlight/back_issues/095";
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DR   EMBL; X17079; CAA34932.1; -; Genomic_DNA.
DR   EMBL; M60398; AAA25020.1; -; Genomic_DNA.
DR   EMBL; AB032429; BAA84532.1; -; Genomic_DNA.
DR   EMBL; AE000511; AAD07144.1; -; Genomic_DNA.
DR   PIR; A38537; URKCAP.
DR   RefSeq; NP_206873.1; NC_000915.1.
DR   RefSeq; WP_000779223.1; NC_018939.1.
DR   PDB; 1E9Y; X-ray; 3.00 A; A=1-238.
DR   PDB; 1E9Z; X-ray; 3.00 A; A=1-238.
DR   PDB; 6QSU; EM; 2.40 A; A/C/E/G/I/K/M/O/Q/S/U/W=1-238.
DR   PDB; 6ZJA; EM; 2.00 A; A/C/E/G/I/K/M/O/Q/S/U/W=1-238.
DR   PDB; 8HC1; EM; 2.30 A; A/E/I/M/Q/U/Y/c/g/k/o/s=1-238.
DR   PDBsum; 1E9Y; -.
DR   PDBsum; 1E9Z; -.
DR   PDBsum; 6QSU; -.
DR   PDBsum; 6ZJA; -.
DR   PDBsum; 8HC1; -.
DR   AlphaFoldDB; P14916; -.
DR   EMDB; EMD-11233; -.
DR   EMDB; EMD-34648; -.
DR   EMDB; EMD-4629; -.
DR   SMR; P14916; -.
DR   DIP; DIP-3146N; -.
DR   IntAct; P14916; 7.
DR   MINT; P14916; -.
DR   STRING; 85962.HP_0073; -.
DR   BindingDB; P14916; -.
DR   ChEMBL; CHEMBL3885651; -.
DR   PaxDb; 85962-C694_00355; -.
DR   DNASU; 900171; -.
DR   EnsemblBacteria; AAD07144; AAD07144; HP_0073.
DR   KEGG; hpy:HP_0073; -.
DR   PATRIC; fig|85962.47.peg.77; -.
DR   eggNOG; COG0831; Bacteria.
DR   eggNOG; COG0832; Bacteria.
DR   InParanoid; P14916; -.
DR   OrthoDB; 9797217at2; -.
DR   PhylomeDB; P14916; -.
DR   BioCyc; MetaCyc:HP_RS00370-MONOMER; -.
DR   BRENDA; 3.5.1.5; 2604.
DR   SABIO-RK; P14916; -.
DR   UniPathway; UPA00258; UER00370.
DR   EvolutionaryTrace; P14916; -.
DR   PHI-base; PHI:7264; -.
DR   Proteomes; UP000000429; Chromosome.
DR   GO; GO:0035550; C:urease complex; IEA:InterPro.
DR   GO; GO:0016151; F:nickel cation binding; IEA:InterPro.
DR   GO; GO:0009039; F:urease activity; IEA:UniProtKB-UniRule.
DR   GO; GO:0043419; P:urea catabolic process; IMP:CACAO.
DR   CDD; cd00407; Urease_beta; 1.
DR   CDD; cd00390; Urease_gamma; 1.
DR   Gene3D; 2.10.150.10; Urease, beta subunit; 1.
DR   Gene3D; 3.30.280.10; Urease, gamma-like subunit; 1.
DR   HAMAP; MF_01954; Urease_beta; 1.
DR   HAMAP; MF_01955; Urease_beta_gamma; 1.
DR   InterPro; IPR002019; Urease_beta-like.
DR   InterPro; IPR036461; Urease_betasu_sf.
DR   InterPro; IPR008223; Urease_gamma-beta_su.
DR   InterPro; IPR002026; Urease_gamma/gamma-beta_su.
DR   InterPro; IPR036463; Urease_gamma_sf.
DR   NCBIfam; TIGR00192; urease_beta; 1.
DR   NCBIfam; TIGR00193; urease_gam; 1.
DR   PANTHER; PTHR33569; UREASE; 1.
DR   PANTHER; PTHR33569:SF1; UREASE; 1.
DR   Pfam; PF00699; Urease_beta; 1.
DR   Pfam; PF00547; Urease_gamma; 1.
DR   PIRSF; PIRSF001225; Urease_gammabeta; 1.
DR   SUPFAM; SSF51278; Urease, beta-subunit; 1.
DR   SUPFAM; SSF54111; Urease, gamma-subunit; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Cytoplasm; Direct protein sequencing; Hydrolase;
KW   Reference proteome; Virulence.
FT   CHAIN           1..238
FT                   /note="Urease subunit alpha"
FT                   /id="PRO_0000098075"
FT   REGION          1..102
FT                   /note="Urease gamma"
FT   REGION          103..238
FT                   /note="Urease beta"
FT   CONFLICT        14
FT                   /note="H -> S (in Ref. 5; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        37
FT                   /note="A -> R (in Ref. 1; CAA34932)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        49
FT                   /note="A -> R (in Ref. 1; CAA34932)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        132..133
FT                   /note="KN -> PP (in Ref. 1; CAA34932)"
FT                   /evidence="ECO:0000305"
FT   HELIX           5..25
FT                   /evidence="ECO:0007829|PDB:6ZJA"
FT   HELIX           32..49
FT                   /evidence="ECO:0007829|PDB:6ZJA"
FT   HELIX           54..60
FT                   /evidence="ECO:0007829|PDB:6ZJA"
FT   HELIX           61..63
FT                   /evidence="ECO:0007829|PDB:6ZJA"
FT   HELIX           67..69
FT                   /evidence="ECO:0007829|PDB:6ZJA"
FT   HELIX           74..77
FT                   /evidence="ECO:0007829|PDB:6ZJA"
FT   STRAND          79..87
FT                   /evidence="ECO:0007829|PDB:6ZJA"
FT   STRAND          90..97
FT                   /evidence="ECO:0007829|PDB:6ZJA"
FT   STRAND          118..121
FT                   /evidence="ECO:0007829|PDB:6ZJA"
FT   STRAND          127..133
FT                   /evidence="ECO:0007829|PDB:6ZJA"
FT   STRAND          135..137
FT                   /evidence="ECO:0007829|PDB:6ZJA"
FT   STRAND          139..142
FT                   /evidence="ECO:0007829|PDB:6ZJA"
FT   HELIX           147..149
FT                   /evidence="ECO:0007829|PDB:6ZJA"
FT   STRAND          154..156
FT                   /evidence="ECO:0007829|PDB:6ZJA"
FT   HELIX           158..161
FT                   /evidence="ECO:0007829|PDB:6ZJA"
FT   STRAND          164..166
FT                   /evidence="ECO:0007829|PDB:6ZJA"
FT   STRAND          173..176
FT                   /evidence="ECO:0007829|PDB:6ZJA"
FT   STRAND          181..188
FT                   /evidence="ECO:0007829|PDB:6ZJA"
FT   HELIX           208..220
FT                   /evidence="ECO:0007829|PDB:6ZJA"
SQ   SEQUENCE   238 AA;  26540 MW;  4E77328669CD9A2D CRC64;
     MKLTPKELDK LMLHYAGELA KKRKEKGIKL NYVEAVALIS AHIMEEARAG KKTAAELMQE
     GRTLLKPDDV MDGVASMIHE VGIEAMFPDG TKLVTVHTPI EANGKLVPGE LFLKNEDITI
     NEGKKAVSVK VKNVGDRPVQ IGSHFHFFEV NRCLDFDREK TFGKRLDIAS GTAVRFEPGE
     EKSVELIDIG GNRRIFGFNA LVDRQADNES KKIALHRAKE RGFHGAKSDD NYVKTIKE
//